The importance of altered beta cell function in the primary pathophysiology of non-insulin dependent diabetes mellitus (NIDDM) is uncertain. The proposed studies aim to test the hypothesis that states of glucose intolerance are characterized by: 1) alterations in the relationships between glucose and insulin secretion; 2) reduced insulin secretory responses to non-glucose secretogogues which act at different points in the insulin secretory cascade and 3) reductions in the ability of the beta cell to adapt normally to the presence of insulin resistance or mild hyperglycemia. Studies will also be performed to determine the extent to which these defects are reversible by treatment of the glucose intolerance and whether the absence of regular oscillations in peripheral insulin reduces the effectiveness of secreted insulin, thereby aggravating the state of insulin resistance which is present in many subjects with impaired glucose tolerance and NIDDM. In this context we will specifically determine whether insulin is more efficient in lowering plasma glucose levels when administered as a series of regular oscillations every 120 minutes rather than at a constant rate.